OBJECTIVE: To investigate possible mechanisms to account for reduced tumorigenicity of cells with acquired resistance to actinomycin D and other cancer chemotherapeutic agents. APPROACH: Development and characterization of drug resistant sublines of Chinese hamster and syngeneic mouse tumor cells grown in cell culture will be continued. Agents used are actinomycin D, vincristine, daunomycin, and ethidium bromide. Parameters to be studied include tumorigenicity, morphology, saturation density, and fibrinolytic activity. Since we are accumulating considerable evidence that resistance to these agents and the concomitantly reduced oncogenic potential of the drug-resistant cells are mediated by the cell membrane, we plan also to determine whether there are antigenic differences between tumorigenic, drug-sensitive cells and the less tumorigenic, drug-resistant derivatives.